Hoe patiëntspecifieke modellering de bestraling van levertumoren kan verbeteren
Hepatocellulair carcinoom (HCC) is de meest voorkomende vorm van leverkanker en de op twee na belangrijkste oorzaak van kanker gerelateerde sterfgevallen wereldwijd. Wanneer het wegsnijden van de tumor geen optie is, wordt HCC vaak behandeld met transarteriële radio-embolisatie (TARE). Tijdens deze behandeling wordt een katheter in de leverslagader ingebracht en worden radioactieve partikels geïnjecteerd om de tumor te bestralen. Omdat de straling hoofdzakelijk op de tumor gericht is, kunnen in vergelijking met andere behandelingen hogere en effectievere stralingsdoses worden gebruikt.
Figuur 1: TARE-procedure. (Bron: [9])
Patiëntspecifieke simulaties
Hoe de partikels zich verspreiden in de patiënt en hoeveel dosis de tumor en de lever toebedeeld krijgen, hangt af van meerdere variabelen. Zo spelen de geometrie van de slagaders, die heel patiëntspecifiek is, en de katheterlocatie een belangrijke rol, alsook de snelheid, de hoek en de timing van de injectie. Daarnaast kan ook de diameter en de densiteit van de partikels de distributie beïnvloeden. Om de stroming van het bloed en de partikels in de slagaders te simuleren kan men gebruik maken van computational fluid dynamics (CFD)-simulaties. Uit deze simulaties verkrijgt men de partikeldistributie waardoor men kan afleiden hoeveel partikels door elke slagader stromen en of deze naar de tumor of de lever gaan. Door te variëren met de parameters kan de behandeling geoptimaliseerd worden om zo veel mogelijk partikels naar de tumor te sturen en niet naar de gezonde lever. De arts weet dan op welke positie de katheter moet geplaatst worden en met welke snelheid hij de partikels best injecteert.
De optimale dosis?
Echter, uit de partikeldistributie kan men geen informatie afleiden over de geabsorbeerde dosis van tumor, lever en andere omliggende organen. Partikels kunnen namelijk, naast de diameter en de dichtheid, ook variëren door de aangewende radioactieve bron, ook wel radionuclide genoemd. Radionucliden verschillen van elkaar in radioactief verval, halveringstijd en energie, factoren die de dosisverdeling sterk beïnvloeden. Om het verval van de partikels te simuleren kunnen Monte Carlo simulaties toegepast worden. Hierbij wordt het verval niet één keer, maar vele malen gesimuleerd. Daardoor kan men niet alleen de dosisverdeling, maar ook de probabiliteit ervan bepalen.
Doel van het onderzoek
In dit onderzoek wordt de invloed van het type partikel op de dosisverdeling onderzocht voor een patiëntspecifieke case. Dit gebeurt aan de hand van Monte Carlo simulaties op basis van via CFD-simulaties verkregen partikeldistributies. De CFD-simulaties maken gebruik van een hybride partikel-stromingsmodel. Dit houdt in dat de partikels alleen worden gemodelleerd in de eerste paar vertakkingen; daarna wordt aangenomen dat ze de bloedstroom volgen. Daarnaast wordt ook gewerkt met een CT-scan van de patiënt om rekening te houden met de patiëntspecifieke dichtheden en weefsels.
De dosisverdeling van vijf verschillende radionucliden wordt met elkaar vergeleken, met name yttrium-90 (Y-90), holmium-166 (Ho-166), renium-188 (Re-188), lutetium-177 (Lu-177) en fosfor-32 (P-32). Daarnaast richt het onderzoek zich ook op de drie commercieel verkrijgbare partikels: SIR-Spheres (Y-90), TheraSpheres (Y-90) en QuiremSpheres (Ho-166). Deze verschillen immers ook in diameter en dichtheid.
De optimale dosis!
De resultaten tonen aan dat voor een specifieke patiënt de gebruikelijke aanbevolen dosimetriemodellen de vereiste activiteit overschatten en een hogere tumordosis leveren dan nodig. Het gevolg is echter ook dat de dosis die de lever ondergaat ook overschat wordt. De resultaten suggereren zelfs dat de drempeldosis van de lever waarschijnlijk overschreden zal worden met de voorgestelde dosis.
Daarnaast blijkt dat binnen de commercieel verkrijgbare partikels de QuiremSpheres de beste optie zijn voor de behandeling van de gesimuleerde patiënt. Globaal genomen blijkt dat Lu-177 gecombineerd met partikels met een diameter van 30 µm en een dichtheid van 1,4 g/cm³ de meest effectieve behandelingsoptie is. Vergeleken met de andere radionucliden en partikeldistributies levert het de hoogste geabsorbeerde tumordosis terwijl het meeste gezonde leverweefsel gespaard blijft.
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